PROJECT SUMMARY The candidate, a consultant in the Department of Cardiovascular Diseases, a Professor of Medicine at Mayo Clinic College of Medicine, Chair of the Mayo Cardiovascular Genomics Task Force, and an established clinician-scientist, is applying for a Mid-Career Investigator Award in Patient-Oriented Research (POR) to expand his mentorship and research program in cardiovascular genomics. Dr. Kullo's prior mentoring experience, his publication and funding record together with his research support in EHR-based genomic discovery and implementation demonstrate his commitment and passion for POR and provide a robust foundation to accomplish the goals and objectives of the K24 Award. The specific aims of this application address the purpose of the K24 Award and are: 1) To provide Dr. Kullo with protected time to mentor junior investigators from existing training programs and the pool of residents, fellows, and faculty at Mayo with the goal to develop them into independent clinical researchers in cardiovascular genomics; 2) To increase his effectiveness as a mentor by continued training in the responsible conduct of research and developing expertise in advanced techniques in precision medicine, implementation science and learning health systems; and 3) To enable Dr. Kullo to expand a program that combines innovative POR in cardiovascular genomics and that provides an ideal environment to develop future leaders in this area. The Principal Investigator has a substantial track record of mentoring trainees and junior faculty in POR (>60 mentees whose awards include a K01, a KL2, AHA postdoctoral fellowship and numerous intramural grants). The K24 award would provide protected time for the Principal Investigator to expand and enhance these efforts. The mentoring plan capitalizes on his current mentoring activities and numerous collaborative research projects to develop a career development path for a new generation of investigators capable of integrating cutting-edge methods at the interface of precision medicine, implementation science and learning health systems. A diverse portfolio of currently funded research opportunities exists for mentees to gain experience in POR and develop their own independent research directions. The mentoring plan includes an individualized research project in POR, scheduled mentor meetings, close collaboration with a multidisciplinary team of investigators, formal educational in statistics & the responsible conduct of research, and scheduled formal feedback from a mentoring team. The clinical research infrastructure at Mayo is unparalleled and together with resources of the eMERGE network, will provide a rich training environment for mentees. The new research component of the application will include a genomic study of cascade screening in patients with familial hypercholesterolemia (FH) who do not have an identifiable mutation in the known FH gene.